The approaches described in this section could be pursued but are not necessarily approaches that have previously been conceived or pursued. Therefore, unless otherwise indicated, it should not be assumed that any of the approaches described in this section qualify as prior art merely by virtue of their inclusion in this section.
Chemical polymorph detection, identification, and analysis may be an important process in many industries that rely on formulation, inspection, analysis, or process/quality control of chemicals or materials, for example, in pharmaceuticals, petrochemicals, electronics, solar technology and photovoltaics, food processing, industrial chemicals, and so forth. Additionally, reliable and reproducible detection, analysis, formulation, manufacturing or testing of materials, such as biological, chemical, semiconductors, geological materials, may require both chemical and structural analysis of the substance. Currently, various spectroscopic techniques may be used to attempt to identify chemical constituents, including mass spectroscopy (MS), Fourier transform infrared (FT-IR), near-infrared (FT-NIR) spectroscopy, Terahertz (THz, or far-IR) spectroscopy, and Raman spectroscopy.
Various techniques may be used to identify characteristics related to material structure (e.g., crystal structure and polymeric chain orientation), including x-ray diffraction (XRD), THz spectroscopy, scanning electron microscopy (SEM), and atomic force or scanning probe microscopy (AFM/SPM).
Typically, Raman and infrared (IR) spectroscopic techniques measure spectral signals, also referred to as “Raman shifts”, across what is referred to a “fingerprint region” ranging from ˜200 cm−1 to 5,000 cm−1 (or 6 THz-150 THz), where the shifts (measured relative to an excitation wavelength) have been correlated to specific vibration energies associated with various chemical bonds, leading to a decipherable signature related to the chemical composition of the substance. After measurements are taken, a library of reference spectra may be used for comparison, and, furthermore, sophisticated algorithms may be used to analyze both the composition and concentration of compounds.
Low frequency Raman shifts, which also correspond to what is referred to as “THz-regime” frequencies (defined as ranging from ˜5 cm−1 to 200 cm−1, or 150 GHz to 6 THz), have been shown to provide additional information (beyond chemical composition) relating to specific lattice vibrations or “phonon modes” that are indicative of molecular structure, and therefore are more directly informative about crystal lattices or polymeric chain orientations, as well as intermolecular interactions of molecules. These low frequency/THz spectra, also referred to as THz-Raman spectra, may be used to rapidly and clearly distinguish polymorphs, allotropes, conformers, or other structurally distinctive attributes of materials in a variety of substances, including pharmaceuticals, plastics and polymers, industrial chemicals, explosive and hazardous materials, nano-materials, biological tissues, and so forth.
However, these frequencies, which reside extremely close to the Rayleigh (or excitation) wavelength, have been both difficult and expensive to access with traditional Raman spectrometer systems. Rayleigh attenuation is critical to all Raman systems, since the process of Raman scattering is extremely inefficient, in particular, only about 1×10−9 of the incident photons will produce a Raman signal. Accordingly, in order to resolve these extremely weak signals, the excitation wavelength typically needs to be attenuated with a filter achieving an optical density (OD) of OD 8.
Most commercial Raman systems utilize thin film edge filters to completely remove the Rayleigh excitation. The thin film edge filters may cut off all signals below about 150-200 cm−1 from the Rayleigh line, blocking both low frequencies and the entire anti-Stokes region. Some systems utilize notch filters (either thin-film or holographic), which can enable capture of anti-Stokes signals, but limitations on their transition bandwidth also result in blocking low-frequency signals. These systems are well suited to examining higher-energy molecular transitions (from ˜200 cm−1 to 2,500 cm−1) for chemical composition, with sufficiently broad range and spectral resolution (˜5 to 10 cm−1 or 150 to 300 GHz) for most chemical identification and analysis applications, but cannot capture low-frequency signals.
Multi-stage, or cascaded, spectrometer systems have been the traditional means for achieving extremely high Rayleigh reduction while preserving the low-frequency signals that are close to the laser line, but these traditional systems significantly increase the size and complexity of the system, while greatly reducing the overall Raman signal as well. Therefore, low-frequency measurements may take extremely long periods and may be susceptible to poor signal-to-noise ratios (SNR). These systems may be also quite large, expensive and require a great deal of expertise to operate, thus limiting their usefulness in a manufacturing or field environment.
THz spectroscopy systems, on the other hand, are based on absorption of a generated THz-frequency signal (vs. Raman scattering) and capable of probing the same “low frequency/THz” energy regimes, but are generally constrained to a small spectral range (0-4 THz), limiting their ability to see the complete “fingerprint region” or chemical composition of a substance. THz spectroscopy techniques may also require special sample preparation, temperature control, and/or may be susceptible to moisture and water content, as well as being relatively expensive compared to the other techniques.
Finally, XRD systems may be extremely useful for determining the atomic and molecular structure of a crystal or biological molecule, but typically require significant sample preparation and are destructive in nature, therefore limiting their use in many manufacturing and process control applications.